The amounts of immunoreactive proinsulin (IRP), immunoreactive insulin (IRI), and C-peptidelike immunoreactivity (CPR) in six insulinomas and one nesidioblastosis lesion were determined together with those in the surrounding pancreatic tissue. Four non-insulinoma and nondiabetic human pancreases were used as the control. The IRP in the seven tumors ranged from 5.85 micrograms/g to 65.45 micrograms/g (mean +/- SEM, 28.70 +/- 8.01 micrograms/g), while the IRP in the surrounding pancreatic tissue ranged from 2.08 micrograms/g to 11.71 micrograms/g (5.32 +/- 1.76 micrograms/g). Control pancreases had an IRP content of 12.01 +/- 2.36 micrograms/g. The IRI in the seven tumors ranged from 4.02 U/g to 47.97 U/g (14.40 +/- 6.35 U/g), while that in the surrounding pancreatic tissue ranged from 0.28 U/g to 3.64 U/g (2.32 +/- 0.63 U/g). Mean tumor CPR was 206.84 +/- 81.6 micrograms/g and it was 29.16 +/- 9.15 micrograms/g in the surrounding pancreatic tissue. The molar ratio of the IRP to IRI content was 6.83 +/- 1.95% for tumor tissue and 6.24 +/- 2.18% for the surrounding pancreatic tissue. These levels were similar to the ratio in the control pancreases (7.67 +/- 1.88%), in contrast to the higher serum IRP/IRI ratio in the tumor patients.